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Stroke and Vascular Neurology Jun 2024The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.
BACKGROUND
The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.
OBJECTIVE
We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.
METHODS
In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining.
RESULTS
The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5-6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration.
CONCLUSIONS
Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.
PubMed: 38906547
DOI: 10.1136/svn-2023-002962 -
Mechanisms of Ageing and Development Jun 2024Psychological stress is a major contributing factor to several health problems (e.g., depression, cardiovascular disease). Around 35 % of the world's population...
Psychological stress is a major contributing factor to several health problems (e.g., depression, cardiovascular disease). Around 35 % of the world's population suffers from it, including younger generations. Physiologically, stress manifests through neuroendocrine pathways (Hypothalamic-Pituitary-Adrenal (HPA) axis and Sympathetic-Adrenal-Medullary (SAM) system) which culminate in the production of stress mediators like cortisol, epinephrine and norepinephrine. Stress and its mediators have been associated to body aging, through molecular mechanisms such as telomere attrition, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysbiosis, among others. Regarding its impact in the skin, stress impacts its structural integrity and physiological function. Despite this review focusing on several hallmarks of aging, emphasis was placed on skin microbiota dysbiosis. In this line, several studies, comprising different age groups, demographic contexts and body sites, have reported skin microbiota alterations associated with aging, and some effects of stress mediators on skin microbiota have also been reviewed in this paper. From a different perspective, since it is not a "traditional" stress mediator, oxytocin, a cortisol antagonist, has been related to glucorticoids inhibition and to display positive effects on cellular aging. This hormone dysregulation has been associated to psychological issues such as depression, whereas its upregulation has been linked to positive social interaction.
PubMed: 38906383
DOI: 10.1016/j.mad.2024.111956 -
Biomedicine & Pharmacotherapy =... Jun 2024Osteoporosis, characterized by compromised bone density and microarchitecture, represents a significant global health challenge, particularly in aging populations. This... (Review)
Review
Osteoporosis, characterized by compromised bone density and microarchitecture, represents a significant global health challenge, particularly in aging populations. This comprehensive review delves into the intricate signaling pathways implicated in the pathogenesis of osteoporosis, providing valuable insights into the pivotal role of signal transduction in maintaining bone homeostasis. The exploration encompasses cellular signaling pathways such as Wnt, Notch, JAK/STAT, NF-κB, and TGF-β, all of which play crucial roles in bone remodeling. The dysregulation of these pathways is a contributing factor to osteoporosis, necessitating a profound understanding of their complexities to unveil the molecular mechanisms underlying bone loss. The review highlights the pathological significance of disrupted signaling in osteoporosis, emphasizing how these deviations impact the functionality of osteoblasts and osteoclasts, ultimately resulting in heightened bone resorption and compromised bone formation. A nuanced analysis of the intricate crosstalk between these pathways is provided to underscore their relevance in the pathophysiology of osteoporosis. Furthermore, the study addresses some of the most crucial long non-coding RNAs (lncRNAs) associated with osteoporosis, adding an additional layer of academic depth to the exploration of immune system involvement in various types of osteoporosis. Finally, we propose that SKP1 can serve as a potential biomarker in osteoporosis.
PubMed: 38906027
DOI: 10.1016/j.biopha.2024.116954 -
Thrombosis Research Jun 2024The prevalence of anticoagulation treatment is increasing as an aging global population faces a high burden of cardiovascular comorbidities. Direct oral anticoagulants,...
BACKGROUND
The prevalence of anticoagulation treatment is increasing as an aging global population faces a high burden of cardiovascular comorbidities. Direct oral anticoagulants, including factor Xa inhibitors (FXai), are replacing vitamin K antagonists as the most commonly prescribed treatment for reducing risk of thrombotic events. While the risk of FXai-associated spontaneous bleeds is established, less is understood about their management and the effect of treatment on clinical and patient-reported outcomes. The primary objectives of the REVERXaL study are to describe patient characteristics, health care interventions during the acute-care phase, in-hospital outcomes, and associations between timing of reversal/replacement agent administration and in-hospital outcomes. Secondary/exploratory objectives focus on clinical assessments and patient-reported outcome measures (PROMs) at 30 and 90 days.
METHODS
REVERXaL is a multinational, observational study of hospitalized patients with FXai-associated major bleeds in Germany, Japan, the United Kingdom, and the United States. The study includes 2 cohorts of approximately 2000 patients each. Cohort A is a historic cohort for whom medical chart data will be collected from hospitalization to discharge for patients admitted for major bleeds during FXai use within 2 years prior to enrollment of Cohort B. Cohort B will prospectively enroll patients administered any reversal/replacement agent during hospitalization to manage FXai-associated major bleeds and will include the collection of clinical outcomes and PROMs data over 3 months.
CONCLUSIONS
REVERXaL will generate insights on patient characteristics, treatment approaches, and associated outcomes in patients hospitalized with FXai-associated major bleeds. These data may inform clinical practice and streamline treatment pathways in this population.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; unique identifier: NCT06147830.
PubMed: 38905928
DOI: 10.1016/j.thromres.2024.109046 -
EBioMedicine Jun 2024Metabolic ageing biomarkers may capture the age-related shifts in metabolism, offering a precise representation of an individual's overall metabolic health.
BACKGROUND
Metabolic ageing biomarkers may capture the age-related shifts in metabolism, offering a precise representation of an individual's overall metabolic health.
METHODS
Utilising comprehensive lipidomic datasets from two large independent population cohorts in Australia (n = 14,833, including 6630 males, 8203 females), we employed different machine learning models, to predict age, and calculated metabolic age scores (mAge). Furthermore, we defined the difference between mAge and age, termed mAgeΔ, which allow us to identify individuals sharing similar age but differing in their metabolic health status.
FINDINGS
Upon stratification of the population into quintiles by mAgeΔ, we observed that participants in the top quintile group (Q5) were more likely to have cardiovascular disease (OR = 2.13, 95% CI = 1.62-2.83), had a 2.01-fold increased risk of 12-year incident cardiovascular events (HR = 2.01, 95% CI = 1.45-2.57), and a 1.56-fold increased risk of 17-year all-cause mortality (HR = 1.56, 95% CI = 1.34-1.79), relative to the individuals in the bottom quintile group (Q1). Survival analysis further revealed that men in the Q5 group faced the challenge of reaching a median survival rate due to cardiovascular events more than six years earlier and reaching a median survival rate due to all-cause mortality more than four years earlier than men in the Q1 group.
INTERPRETATION
Our findings demonstrate that the mAge score captures age-related metabolic changes, predicts health outcomes, and has the potential to identify individuals at increased risk of metabolic diseases.
FUNDING
The specific funding of this article is provided in the acknowledgements section.
PubMed: 38905750
DOI: 10.1016/j.ebiom.2024.105199 -
Medicine Jun 2024Along with global aging, osteoarthritis (OA) appears to have a high incidence and disability rate, which seriously affects the quality of life of patients, making age a...
Along with global aging, osteoarthritis (OA) appears to have a high incidence and disability rate, which seriously affects the quality of life of patients, making age a major risk factor. However, the pathology of OA is under-researched, and there is no obvious and effective treatment. Research has demonstrated the importance of aging, inflammation, and immunology in the onset and course of OA. This study aims to anticipate therapeutic drugs based on critical genes associated with OA and to elucidate the roles of genes and possible biomarkers associated with inflammation, immunology, and cellular senescence in OA. The OA gene expression matrix was first obtained from the Gene Expression Omnibus database. Screening for OA significant differentially expressed genes by bioinformatics identification. Specific biological processes and related signaling pathways of the differential genes were enriched. Then elucidate the status of immune cell involvement in OA based on immune infiltration analysis. Finally predict therapeutic agents based on pivotal genes. A total of 198 differentially expressed genes were identified in OA, and TP53, EGFR, TGFB1, LEP, CD4, MAPK8, SCARB1, ADIPOQ, JAK2, and SERPINE1 were further identified as important hub genes. The enrichment results showed that the development of arthritis was mainly related to immune cell differentiation, amino acid metabolism and cellular senescence process. The validation of immune infiltration results indicated that NK_cells, CD4_Tcells, Macrophages, Monocytic_lineage, Dendritic_cells, Basophils, CD8+_naive_T-cells may play an important role in the immune process of OA. Key Drug Prediction of Hub Genes found that Halicin, Ruxolitinib, Tofacitinib, Clenoliximab, Baricitinib may be a key drug or component in the treatment of OA.
Topics: Humans; Osteoarthritis; Computational Biology; Biomarkers; Gene Expression Profiling; Piperidines; Pyrimidines; Pyrroles
PubMed: 38905428
DOI: 10.1097/MD.0000000000038430 -
Medicine Jun 2024Frailty is an important public health concern associated with aging. It increases the risk of adverse clinical outcomes, such as falls, late-life dependency,... (Observational Study)
Observational Study
Frailty is an important public health concern associated with aging. It increases the risk of adverse clinical outcomes, such as falls, late-life dependency, hospitalization, disability, and mortality. The objectives of this study were to estimate the prevalence of frailty and to identify factors associated with frailty among older adults (≥65 years) admitted to King Abdulaziz University Hospital, Jeddah, Saudi Arabia. This cross-sectional study was conducted at King Abdulaziz University Hospital. The data were collected during the months of January and February 2022 and included demographic characteristics, comorbidities, length of stay, and hospital mortality. Frailty status of participants was assessed using the Clinical Frailty Scale. A total of 147 patients (aged ≥ 65 years) were included in our study. The prevalence rates of frailty and non-frailty were 71.4% and 28.6%, respectively. Frail patients had higher comorbidity index (P = .003), polypharmacy (P = .003), heart failure (P = .001), and prolonged hospital stays (P = .007). The results of the multiple logistic regression revealed that the tall patients had a lower risk of frailty (odds ratio = 0.0089, 95% confidence interval: 0.0001-0.7588, P = .042) and patients with higher comorbidity indexes had higher risk of frailty (odds ratio = 1.4907, 95% confidence interval: 1.1449-1.9927, P = .004). In this study, more than two-thirds of the hospitalized older patients were classified as frail. High comorbidity index, heart failure, and polypharmacy were strong predictors of frailty. Patients with frailty were more likely to have a prolonged hospital stay than those without frailty. Therefore, early detection of frailty and proper intervention are essential for improving health outcomes in this vulnerable population.
Topics: Humans; Saudi Arabia; Aged; Male; Cross-Sectional Studies; Female; Frailty; Hospitalization; Aged, 80 and over; Frail Elderly; Hospitals, Teaching; Prevalence; Length of Stay; Comorbidity; Geriatric Assessment; Risk Factors; Polypharmacy; Hospital Mortality
PubMed: 38905424
DOI: 10.1097/MD.0000000000038603 -
PloS One 2024Foster families may represent an alternative model for dependent older adults in many countries where nursing homes are insufficiently developed. This study aimed to...
BACKGROUND
Foster families may represent an alternative model for dependent older adults in many countries where nursing homes are insufficiently developed. This study aimed to assess the prevalence of malnutrition and its determinants in older adults living in foster families in Guadeloupe (French West Indies).
METHODS
This cross-sectional study was gathered from the KASAF (Karukera Study of Ageing in Foster families) study (n = 107, 41M/66F, Mdn 81.8 years). Nutritional status was assessed with the Mini Nutritional Assessment Short-Form (MNA-SF). Clinical characteristics and scores on geriatric scales (Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Short Physical Performance Battery (SPPB), Center for Epidemiologic Studies- Depression (CESD) and Questionnaire Quality of Life Alzheimer's Disease (QoL-AD)) were extracted. Bivariate analysis and logistic models adjusted for age and gender were performed to test the association of nutritional status with socio-demographic variables and geriatric scales.
RESULTS
Thirty (28.0%) older adults were malnourished (MNA-SF score ≤7). In bivariate analysis, malnutrition was associated with an increased prevalence of cardiovascular diseases (46.7% versus 19.5%, p = 0.004), the presence of hemiplegia (30.0% versus 6.5%, p = 0.003), a poorer cognitive status (MMSE score 4.7 ± 7.1versus 9.7 ± 10.7; p = 0.031), higher risk of depression (CESD score 27.3 ± 23.0 versus 13.5 ± 14.4; p = 0.035) and dependency (ADL score 1.9 ± 1.9 versus 2.3 ± 2.1; p<0.001). Malnutrition was also associated with lower caregivers'rating of QoL (QoL-AD score 21.8 ± 6.4 versus 26.0 ± 5.7; p = 0.001) but not by older adult's rating (24.1 ± 11.2 versus 28.3 ± 7.7; p = 0.156). Similar associations were observed in logistic models adjusted for age and gender.
CONCLUSION
Malnutrition was common among foster families for older adults. Special attention towards the prevention and treatment of malnutrition in older adults from cardiovascular diseases, cognitive impairment, dependency and depression is necessary in this model of dependency support.
Topics: Humans; Male; Female; Malnutrition; Cross-Sectional Studies; Aged; Aged, 80 and over; Guadeloupe; Nutritional Status; Geriatric Assessment; Prevalence; Activities of Daily Living; Quality of Life; Nutrition Assessment; Depression
PubMed: 38905295
DOI: 10.1371/journal.pone.0304998 -
PloS One 2024In the context of global aging, promoting the health of the elderly has become a critical issue. However, whether the development of smart cities can impact the health...
In the context of global aging, promoting the health of the elderly has become a critical issue. However, whether the development of smart cities can impact the health of older adults remains to be further validated. In this paper, based on panel data from the China Health and Retirement Longitudinal Study (CHARLS), a difference in difference model is used to empirically investigate whether smart city construction improves the health of older people in the region. The results show that smart city construction enhances the health of the elderly. Specifically, the construction achieved a significant improvement in the physical health of the elderly who did not live with their children. The health promotion effect of the smart city was more significant for the urban elderly than for the rural elderly. The elucidated mechanisms of influence suggest that smart cities bring about their effects through the promotion of urban leisure infrastructure, enhancement of medical service provision, advancement in urban environmental protection and stimulation of urban information and communication technology infrastructure development.
Topics: Humans; China; Aged; Male; Female; Cities; Longitudinal Studies; Urban Population; Rural Population; Health Promotion; Middle Aged; Aged, 80 and over; City Planning; Health Status
PubMed: 38905258
DOI: 10.1371/journal.pone.0305897 -
PloS One 2024Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain...
Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain mechanisms are less clear, especially in the context of aging. Using fMRI, we aimed to investigate the neural correlates underlying local and global processing in early and late adulthood. We recruited 77 healthy adults aged 19-77 who completed a visual search task based on 2-level hierarchical stimuli made of squares and/or circles. Participants were instructed to detect a target (a square) at either a local (small) or global (large) level of a hierarchical geometrical form, in the presence or absence of other hierarchical geometrical forms (distractors). At the behavioral level, we revealed high accuracy for all participants, but older participants were slower to detect local targets, specifically in presence of distractors. At the brain level, while both local and global processing were associated with occipital activation, local processing also recruited the anterior insula and dorsal anterior cingulate cortex, that are core regions of the salience network. However, while the presence of distractors in the local condition elicited specifically stronger activation within the right anterior insula for the young group, it was not observed for older participants. In addition, older participants showed less activation than younger participants in the occipital cortex, especially for the most complex conditions. Our findings suggest that the brain correlates underlying local and global processing change with aging, especially for complex visual patterns. These results are discussed in terms of top-down reduction effects from the salience network on primary visual areas, that may lead to specific difficulties to process local visual details in older adults.
Topics: Humans; Adult; Male; Female; Middle Aged; Magnetic Resonance Imaging; Aged; Young Adult; Brain Mapping; Visual Perception; Photic Stimulation; Brain; Aging; Reaction Time; Occipital Lobe
PubMed: 38905236
DOI: 10.1371/journal.pone.0303796